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New synthetic form of protein holds promise to stop cancer spread
Date:9/15/2008

the CXCL12 protein interacts with a portion of the CXCR4 receptor. Because previous research on the CXCL12 structure failed to resolve these details, a key step in the spread of metastatic cancer remained poorly understood.

To complete the molecular model for CXCL12 binding to CXCR4, Drs. Volkman and Veldkamp discovered that it was necessary to link two CXCL12 molecules, in effect locking it into a form that could not be chemically separated. This locked form of the protein, known as a dimer, could still bind to the CXCR4 receptor.

However, the locked protein displayed different behavior than the unlocked form. A normal CXCL12 protein strongly induces cell migration, but the locked form of the protein caused no cells to migrate at all.

The researchers then ran another experiment to see what would happen if the normal CXCL12 and locked CXCL12 dimer were combined. The combined molecule had the opposite effect of the single molecule, and it resulted in a near elimination of cell migration. This meant they had discovered that it was possible to convert CXCL12 into a protein that inhibits cell migration.

"This was exciting because it was genuinely unexpected," says Dr. Volkman. "It was the strongest suggestion yet that chemokine dimers might really be active participants in directing the migration of white blood cells and possibly other kinds of cells."

Dr. Volkman says the next step is establishing if the CXCL12 dimer could be effective in inhibiting the spread of cancer. He again turned to the assistance of Dr. Dwinell, who had filed an earlier patent application on the use of CXCL12 in limiting cancer progression. This pending patent also involved a graduate student, Michael Wendt.

"While we were focused on understanding details of the molecular structure of CXCL12, Dr. Dwinell's research group had developed a sophisticated method for measuring breast cancer metastasis," he says. "So we asked him to he
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Contact: Toranj Marphetia
toranj@mcw.edu
414-456-4744
Medical College of Wisconsin
Source:Eurekalert

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